ANTITHROMBOTIC ACTION OF ENDOGENOUS PORCINE PROTEIN-C ACTIVATED WITH A LATENT PORCINE THROMBIN PREPARATION

Endogenously activated protein C is evaluated for antithrombotic activ ity in porcine carotid arteries subjected to mechanical trauma. Protei n C is activated by intravenous administration of guanidinobenzoyl-thr ombin, which binds to thrombomodulin and there deacylates to yield thr ombin. The bound, transiently active thrombin yields a peak of anticoa gulant activity between 5 and 10 min after infusion of the latent thro mbin. Inhibition of thrombin binding in vivo by co-infusing an active- site-blocked thrombin preparation elicits acute and lethal systemic th rombosis. Nearly occlusive platelet thrombosis, which occurs within 30 min of crushing 1 cm segments of carotid arteries with a standard hem ostat, is blocked by endogenous protein C activation initiated 2 min b efore the crush injury. It is concluded that activated protein C block s thrombosis in deeply injured musculo-elastic arteries, and that acti vation of latent thrombin bound to thrombomodulin in vivo is a practic al means for delivery of pharmacologically effective concentrations of activated protein C.